Stable multilineage chimerism without graft versus host disease following nonmyeloablative haploidentical hematopoietic cell transplantation

Robert A. Cina, Krzysztof J. Wikiel, Patricia W. Lee, Andrew M Cameron, Shehan Hettiarachy, Haley Rowland, Jennifer Goodrich, Christine Colby, Thomas R. Spitzer, David M. Neville, Christene A. Huang

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Hematopoietic cell transplantation may offer the only cure for patients with hematological diseases. The clinical application of this therapy has been limited by toxic conditioning and lack of matched donors. Haploidentical transplantation would serve to extend the potential donor pool; however, transplantation across major histocompatibility complex barriers is often associated with severe graft-versus-host disease. Here we evaluate a novel protocol to achieve engraftment across mismatch barriers without toxic conditioning or significant posttransplant complications. METHODS. Nine major histocompatibility complex (MHC)-defined miniature swine received haploidentical hematopoietic cell transplantation following standard myeloablative conditioning. Nine additional animals received haploidentical hematopoietic cell transplantation following a minimally myelosuppressive regimen, consisting of 100 cGy total body irradiation, immunotoxin mediated T-cell depletion, and a short course of cyclosporine. Donor cell engraftment and peripheral chimerism was assessed by polymerase chain reaction and flow cytometry. Graft-versus-host disease was monitored by clinical grading and histology of skin biopsy specimens. RESULTS. All animals conditioned for haploidentical hematopoietic cell transplantation using myeloablative conditioning were euthanized within 2 weeks due to engraftment failure or graft-versus-host disease. All animals conditioned with the nonmyeloablative regimen developed multilineage peripheral blood chimerism during the first 2 months following transplantation. Six animals evaluated beyond 100 days maintained multilineage chimerism in the peripheral blood and lymphoid tissues, showed evidence of progenitor cell engraftment in the bone marrow, and had minimal treatment-related complications. CONCLUSIONS. Here we report that stable multilineage chimerism and engraftment can be established across haploidentical major histocompatibility complex barriers with minimal treatment-related toxicity and without significant risk of graft-versus-host disease.

Original languageEnglish (US)
Pages (from-to)1677-1685
Number of pages9
JournalTransplantation
Volume81
Issue number12
DOIs
StatePublished - Jun 2006
Externally publishedYes

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Chimerism
Cell Transplantation
Graft vs Host Disease
Major Histocompatibility Complex
Transplantation
Poisons
Tissue Donors
Miniature Swine
Immunotoxins
Hematologic Diseases
Whole-Body Irradiation
Lymphoid Tissue
Cyclosporine
Histology
Flow Cytometry
Stem Cells
Therapeutics
Bone Marrow
T-Lymphocytes
Biopsy

Keywords

  • Hematopoietic stem cells
  • Miniature swine
  • Transplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Stable multilineage chimerism without graft versus host disease following nonmyeloablative haploidentical hematopoietic cell transplantation. / Cina, Robert A.; Wikiel, Krzysztof J.; Lee, Patricia W.; Cameron, Andrew M; Hettiarachy, Shehan; Rowland, Haley; Goodrich, Jennifer; Colby, Christine; Spitzer, Thomas R.; Neville, David M.; Huang, Christene A.

In: Transplantation, Vol. 81, No. 12, 06.2006, p. 1677-1685.

Research output: Contribution to journalArticle

Cina, RA, Wikiel, KJ, Lee, PW, Cameron, AM, Hettiarachy, S, Rowland, H, Goodrich, J, Colby, C, Spitzer, TR, Neville, DM & Huang, CA 2006, 'Stable multilineage chimerism without graft versus host disease following nonmyeloablative haploidentical hematopoietic cell transplantation', Transplantation, vol. 81, no. 12, pp. 1677-1685. https://doi.org/10.1097/01.tp.0000226061.59196.84
Cina, Robert A. ; Wikiel, Krzysztof J. ; Lee, Patricia W. ; Cameron, Andrew M ; Hettiarachy, Shehan ; Rowland, Haley ; Goodrich, Jennifer ; Colby, Christine ; Spitzer, Thomas R. ; Neville, David M. ; Huang, Christene A. / Stable multilineage chimerism without graft versus host disease following nonmyeloablative haploidentical hematopoietic cell transplantation. In: Transplantation. 2006 ; Vol. 81, No. 12. pp. 1677-1685.
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AU - Cina, Robert A.

AU - Wikiel, Krzysztof J.

AU - Lee, Patricia W.

AU - Cameron, Andrew M

AU - Hettiarachy, Shehan

AU - Rowland, Haley

AU - Goodrich, Jennifer

AU - Colby, Christine

AU - Spitzer, Thomas R.

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N2 - BACKGROUND. Hematopoietic cell transplantation may offer the only cure for patients with hematological diseases. The clinical application of this therapy has been limited by toxic conditioning and lack of matched donors. Haploidentical transplantation would serve to extend the potential donor pool; however, transplantation across major histocompatibility complex barriers is often associated with severe graft-versus-host disease. Here we evaluate a novel protocol to achieve engraftment across mismatch barriers without toxic conditioning or significant posttransplant complications. METHODS. Nine major histocompatibility complex (MHC)-defined miniature swine received haploidentical hematopoietic cell transplantation following standard myeloablative conditioning. Nine additional animals received haploidentical hematopoietic cell transplantation following a minimally myelosuppressive regimen, consisting of 100 cGy total body irradiation, immunotoxin mediated T-cell depletion, and a short course of cyclosporine. Donor cell engraftment and peripheral chimerism was assessed by polymerase chain reaction and flow cytometry. Graft-versus-host disease was monitored by clinical grading and histology of skin biopsy specimens. RESULTS. All animals conditioned for haploidentical hematopoietic cell transplantation using myeloablative conditioning were euthanized within 2 weeks due to engraftment failure or graft-versus-host disease. All animals conditioned with the nonmyeloablative regimen developed multilineage peripheral blood chimerism during the first 2 months following transplantation. Six animals evaluated beyond 100 days maintained multilineage chimerism in the peripheral blood and lymphoid tissues, showed evidence of progenitor cell engraftment in the bone marrow, and had minimal treatment-related complications. CONCLUSIONS. Here we report that stable multilineage chimerism and engraftment can be established across haploidentical major histocompatibility complex barriers with minimal treatment-related toxicity and without significant risk of graft-versus-host disease.

AB - BACKGROUND. Hematopoietic cell transplantation may offer the only cure for patients with hematological diseases. The clinical application of this therapy has been limited by toxic conditioning and lack of matched donors. Haploidentical transplantation would serve to extend the potential donor pool; however, transplantation across major histocompatibility complex barriers is often associated with severe graft-versus-host disease. Here we evaluate a novel protocol to achieve engraftment across mismatch barriers without toxic conditioning or significant posttransplant complications. METHODS. Nine major histocompatibility complex (MHC)-defined miniature swine received haploidentical hematopoietic cell transplantation following standard myeloablative conditioning. Nine additional animals received haploidentical hematopoietic cell transplantation following a minimally myelosuppressive regimen, consisting of 100 cGy total body irradiation, immunotoxin mediated T-cell depletion, and a short course of cyclosporine. Donor cell engraftment and peripheral chimerism was assessed by polymerase chain reaction and flow cytometry. Graft-versus-host disease was monitored by clinical grading and histology of skin biopsy specimens. RESULTS. All animals conditioned for haploidentical hematopoietic cell transplantation using myeloablative conditioning were euthanized within 2 weeks due to engraftment failure or graft-versus-host disease. All animals conditioned with the nonmyeloablative regimen developed multilineage peripheral blood chimerism during the first 2 months following transplantation. Six animals evaluated beyond 100 days maintained multilineage chimerism in the peripheral blood and lymphoid tissues, showed evidence of progenitor cell engraftment in the bone marrow, and had minimal treatment-related complications. CONCLUSIONS. Here we report that stable multilineage chimerism and engraftment can be established across haploidentical major histocompatibility complex barriers with minimal treatment-related toxicity and without significant risk of graft-versus-host disease.

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